Ischaemia-Reperfusion Injury Contributes to Increased Intestinal Permeability in Severe Acute Pancreatitis.
Abstracts
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Intestinal barrier failure and subsequent bacterial translocation has been implicated in the development of organ dysfunction and septic complications associated with severe acute pancreatitis (AP). Splanchnic hypoperfusion and ischaemia-reperfusion injury (I-R) have been postulated as a cause of increased intestinal permeability. The urinary concentration of Intestinal Fatty Acid Binding Protein (IFABP) has been shown to be a sensitive marker of intestinal ischaemia, with increased levels being associated with I-R. The aim of the current study was to assess the relationship between intestinal permeability, urinary IFABP concentration (IFABP-c), splanchnic ischaemia, and clinical severity. Patients with a clinical and biochemical diagnosis of AP were studied within 72 hours of onset of pain. Polyethylene glycol (PEG) probes of 3350 kDa and 400 kDa were administered enterally and the retrieval ratio (PEG 3350/400) from their renal excretion was used as a measure of intestinal macromolecular permeability. Collected urine was also used to determine IFABP concentration (IFABP-c) and total IFABP excreted (IFABP-t), using an ELISA technique. Systemic inflammatory response was estimated by peak 0-72 hr plasma C-reactive protein level (CRP). Attacks were classified as mild or severe by the Atlanta criteria. Sixty-one patients with AP (19 severe) and 12 healthy controls were studied. Compared to patients with mild attacks, severe attacks were associated with significantly higher PEG excretion ratios (p < 0.0001), PEG 3350 % retrieval (p<0.0001), urinary IFABP-c (medians: 85 ng/ml vs 1086 ng/ml, p < 0.001), and urinary IFABP-t (medians: 210 µg vs. 1143 µg, p = 0.002). Furthermore, the control group had significantly lower IFABP-c (median 37 ng/ml, p = 0.029) and IFABP-t (median 64 µg, p = 0.006), than patients with mild attacks. PEG 3350 % retrieval correlated significantly with IFABP-c (r = 0.50, p < 0.001) and IFABP-t (r = 0.34, p = 0.015), but only IFABP-c correlated significantly with PEG retrieval ratio (3350/400) (r = 0.28, p = 0.04). A strong association was demonstrated between peak CRP and PEG retrieval ratio (r = 0.42, p = 0.002), IFABP-c (r = 0.51, p < 0.001) and FABP-t (r = 0.43, p = 0.001). The results of this study supports the hypothesis that splanchnic hypoperfusion and ischaemia-reperfusion injury contribute to increased intestinal permeability in severe attacks of AP. |
